Background: Oxidative stress in obese people is an important pathogenic mechanism of an obesity-associated metabolic syndrome. We evaluated the association between circulating leptin levels with biomarkers of oxidative stress in overweight and obese participants. Methods: This study was performed on 189 overweight and obese people aged 18-60 years old. Serum leptin, superoxide dismutase (SOD), high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), thiobarbituric acid reactive substances (TBARS) and amyloid A (SAA) concentrations were measured. Pearson correlation and multiple linear regressions were used to assess the relationships. Results: We found that among the biomarkers of oxidative stress and inflammation in participants, serum hs-CRP and SAA were positively correlated with BMI (β=0.003, P<0.001 and β=7.83, P<0.001, respectively). This relationship remained significant even after controlling other oxidative stress and inflammatory indicators (β=0.003, p<0.001 for hs-CRP), but this association disappeared for SAA. In addition, serum hs-CRP was positively correlated with leptin (β=0.001, p=0.003). Regression analysis showed that there was no association between serum Hcy, SAA, TBARS and SOD with serum leptin concentrations Conclusion: Overall, the current study demonstrated that serum hs-CRP and SAA levels were independently correlated with BMI. Furthermore, serum hs-CRP was positively correlated with leptin. Focusing on such strategies may lead to promises for alleviating obesity and its co-morbidities.